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The Formation of Acetyl Co-enzyme A

A large number of molecules that are synthesised in cells are built from two-carbon acetyl groups. An acetyl group derives from ethanoate (acetate) and is named acetyl when it forms a group within a larger molecule. Instead of using free acetate molecules the cell 'activates' the molecule by attaching it to Coenzyme A (CoA).

The acetyl group can derive from pyruvate (and ultimately from monosaccharides if that is the main 'food' for the cell). The two processes of oxidising/decarboxylating pyruvate and attaching the resulting acetyl group to CoA are coupled.

Oxidative decarboxylation is catalyzed by the pyruvate dehydrogenase complex. It is a multimeric assembly of three kinds of enzyme that implements the process in four steps. The animation shows all four steps in sequence and data sheets follow.

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Pyruvate to Hydroxyethyl thiamine pyrophosphate

Enzyme: Pyruvate dehydrogenase component (E1)

Reaction: Oxidative decarboxylation of pyruvate (part1)

Mechanism:The decarboxylation of pyruvate occurs after the combination with TPP.

Prosthetic group: TPP

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Hydroxyethyl thiamine pyrophosphate to Acetyllipoamide

Enzyme: Pyruvate dehydrogenase component (E1)

Reaction: Oxidative decarboxylation of pyruvate (part2)

Mechanism:The oxidation of hydroxyethyl group(-TPP) gives an acetyl group which is transferred to lipoamide. the product is acetyllipoamide.

Prosthetic group: TPP

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Acetyllipoamide to Acetyl CoA and Dihydrolipoamide

Enzyme: Dihydrolipoyl transacetylase (E2)

Reaction: Transfer the acetyl group to CoA

Mechanism:The acetyl group of acetyllipoamide is transferred to CoA, yields acetyl CoA..

Prosthetic group: Lipoamide

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Recycling of Dihydrolipoamide back to Lipoamide

Enzyme: Dihydrolipoyl dehydrogenase (E3)

Reaction: Dehydrogenation of the reduced lipoamide

Mechanism:Two hydrogens of dihydrolipoamide are transferred to FAD and then to NAD. This is the regeneration of oxidized lipoamide..

Prosthetic group: FAD

Creator of Animation: Alisa Sanamontre
Dept Biochemistry, Pramongkutklao College of Medicine,Bangkok,Thailand.
Editor: Jon Maber
Dept Biochemistry & Molecular Biology, The University of Leeds, U.K.
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